The invention relates to the field of pharmaceutical packaging and shipment. In particular, the invention pertains to blister packaging and manufacturing techniques.
Blister packs have been commonly used to package a variety of products or dosage forms in which the individual units of the product are contained or housed separately from each other. Typically, blister packs contain an array or series of blisters positioned in a square or rectangular-shaped film. Each blister contains the product therein and is covered with a lidding or cover layer adhesively secured to the film layer at least at the perimeter of the top of each blister. This lidding seals the blister and protects the contents therein by isolating the contents from the environment.
Blisters in blister packs are typically manufactured by deforming a film layer. Forming the blister in the film is accomplished by hot or cold forming techniques whereby a section of the film is forced into a mold defining a recess having the substantially similar dimensions to the desired shape of the blister to be created. Other blister-forming techniques include blow forming and vacuum forming softened films against a die. Blisters can be produced in a variety of shapes and sizes, and typically come in circular, square or rectangular overall cross-sections.
Blister packs are often used to house or contain a loose product which is relatively robust and capable of withstanding movement within the blister during transportation and storage. Blister packs can also have the dual function as both a mold itself as part of the manufacturing process of the dosage form, as well as the containment and packaging for the in situ molded dosage form. An example of such a technique is disclosed in Thompson et al., U.S. Pat. No. 5,457,895. Accordingly, in situ molded dosage forms can be prepared by depositing the liquid form of the composition directly in the blister and subsequently treating the blister and its contents to the process which solidifies the composition to form the final dosage form. This technique is used to prepare freeze dried or lyophilized dosage forms, for example. The method of producing these in situ formed dosage forms often results in shrinkage of the product thereby producing room for movement of the product inside the blister. Certain dosage forms are relatively fragile or frangible as a result of their manufacturing process and desired administration properties. Such dosage forms include rapidly dissolving oral dosage forms, whereby the dosage form rapidly disintegrates in the patient""s oral cavity.
Blister packs having blisters with narrow openings used to contain solid dosage forms are known, such as those disclosed in Eggert et al., European Patent Application 563 934. These blister packs, however, are not specifically designed for use with frangible pharmaceutical dosage forms, in particular dosage forms molded in situ within the blister. In situ molding techniques for pharmaceutical dosage forms and the blister packs therefore are described in Thompson et al., U.S. Pat. No. 5,457,895 and Heath in PCT WO 00/09313. These blister packs, however, do not prevent the movement of the dosage form within the blister in the space directly beneath the lidding.
During manufacture, unsecured blister contents can often fall out and become damaged during the inspection and sealing stages of the manufacturing process. During in situ molding techniques, the dosage form often shrinks and detaches from the blister walls. Dislodging of blister contents during the sealing process can also interfere with sealing tools and equipment. Another problem associated with blister packs is the damage to the contents as a result of agitation or movement inside the blister that can result from handling, transportation and storage of the pack. This is especially problematic for frangible pharmaceutical products or dosage forms, such as rapidly dissolving oral dosage forms, wherein agitation of the packaging can produce crumbling or fragmenting of the product. Even more challenging is the design of a blister pack which could both confine the movement of frangible contents while at the same time permitting easy removal of the intact dosage form from the blister.
Thus, there exists a need for improved blister packs which restrict the range of movement if its contents without overly inhibiting the intact removal of the contents, especially in the packaging of frangible pharmaceutical products or dosage forms.
The invention described provides a blister pack which confines the movement its contents in order to reduce the likelihood of damage thereto during manufacture, handling and transportation while at the same time permitting easy removal of the contents intact. In particularly, the invention provides a blister pack wherein the blister includes a protruding region between the opening of the blister and the base, thereby producing a constricted portion or xe2x80x9cneckxe2x80x9d near the opening of the blister. In one embodiment, the protruding region of the blister comprises an inwardly directed annulus formed in the blister wall. Accordingly, vertical movement of the contents is confined as a result of the protruding region thereby minimizing the impact on the contents caused by agitation of the blister pack. It has been discovered that a protruding region can be formed in a blister such that both the movement of the contents can be confined, while at the same time permitting easy removal of the contents intact. The invention is particularly useful in the packaging frangible pharmaceutical products, such as freeze dried dosage forms and rapidly dissolving oral dosage forms, and products formed in situ within the blister. It has been further discovered that the invention allows for both the formation of the blister and its use for in situ molding techniques to efficiently prepare and package frangible pharmaceutical products, such as freeze dried dosage forms. Yet another advantage is that the blister packs of the invention hold the frangible dosage form in place and prevent their dislodging during the manufacturing process which commonly occurs from shrinking of the dosage form and physical impact of machinery.
The invention provides for a blister pack for pharmaceutical products comprising a blister formed from a film and having a protruding region between the opening of the blister and its base, the protruding region being adapted to confine the movement of contents placed within the blister. The protruding region can be in the form of an inwardly directed annulus or a plurality of inwardly directed projections on the wall of the blister. The blister pack according to the invention can further comprise an indicia formed on the base of the blister.
The invention further provides for an apparatus for forming a blister from a deformable film and having a protruding region positioned between the opening and base comprising a) a pin having a body, end portion and outer surface, wherein the outer surface contains at least one peripheral recess on said end portion and which defines the protruding region to be formed in the blister, and wherein the end portion defines the base portion of the blister; and b) a die adapted to receive the pin and having a platen, wherein the pin is adapted to transversely contact a film positioned between the pin and die and engage the die in a manner which moves the film inside the die; wherein the peripheral recess on the pin is adapted to permit inward deformation of the film. The apparatus can further comprise at least one indicia forming surface located on the pin face or platen of the die, or both. Furthermore, the apparatus can comprise an air pressure control means for monitoring and controlling the air pressure between the film and chamber of the die during the molding process.
The invention also provides for a method of forming a blister from a film having a protruding region between the opening and the base thereof comprising a) positioning a deformable film between a pin and die, the pin having at least one peripheral recess on its outer surface at the end portion which defines the protruding region of the blister, and engaging the pin and die in a manner whereby the pin defines the blister and the recess on the outer surface of the pin receives a portion of the film and defines the protruding region of the blister.
The invention further provides for a method of packaging a frangible pharmaceutical dosage form comprising depositing the frangible dosage form into a blister having a protruding region between the opening and base of the blister, and covering the blister containing the dosage form to protect the dosage form from the environment.
The invention also provides for a method of forming a freeze dried pharmaceutical dosage form comprising depositing the liquid form of a pharmaceutical composition into a blister having a protruding region between the opening and the base of the blister and freeze drying the liquid composition in situ to form the solid dosage form.